AI Article Synopsis
- - Two series of water-soluble derivatives were created from propofol, and their anesthetic effects were tested in mice while also measuring how quickly propofol was released from these compounds.
- - Compounds in series II, which included structures like γ-hydroxybutyric acid or γ-aminobutyrate, demonstrated a higher therapeutic index and better propofol release rates compared to series I compounds.
- - Among the series II derivatives, compound II-20 showed a therapeutic index of 5.6 and a significantly longer duration of action (571 seconds) without notable toxicity, making it a promising candidate for further research.
Article Abstract
In this work, two series of water-soluble derivatives were designed and synthesized based on the structure of propofol as the lead compound. Furthermore, the anesthetic activities of the synthesized compounds were evaluated in vivo against mice, and the in vitro propofol release rate from five target compounds was determined. The findings of this study have shown that series II compounds which possess the structure feature of propofol + γ-hydroxybutyric acid + α-aminoacetate or γ-aminobutyrate have higher therapeutic index than that of series I compounds which possess the structure feature of propofol + α-aminoacetate or β-aminopropionate. In addition, the rate of propofol released from series II compounds was significantly better than that of series I compounds. Among series II compounds, compound II-20 had a therapeutic index of 5.6 (propofol = 2.7), a duration time of 571 s (propofol = 57 s), and no significant toxicity was observed in vivo, which made it valuable for further development.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2024.129972 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Synthesis, characterization, and photophysical properties of novel 9‑phenyl-9-phosphafluorene oxide derivatives.
Beilstein J Org Chem
December 2024
College of Chemistry and Material Science, Guangdong University of Education, Guangzhou 510303, China.
A novel series of D-A-D-type 9-phenyl-9-phosphafluorene oxide (PhFlOP) derivatives was prepared and is reported herein. The synthetic protocol involved 5 steps from commercially available 2-bromo-4-fluoro-1-nitrobenzene, featuring a noble-metal-free system, mild reaction conditions, and a good yield, especially for the final CsCO-facilitated nucleophilic substitution (77-91% yield). The characterization data obtained from IR and NMR spectroscopy (H, C, F, and P) as well as HRMS spectrometry were in full agreement with the expected structures, and single-crystal X-ray diffraction analysis was conducted to confirm the structure of compound .
View Article and Find Full Text PDFβ-Lactams are the most widely used antibiotics for the treatment of bacterial infections because of their proven track record of safety and efficacy. However, susceptibility to β-lactam antibiotics is continually eroded by resistance mechanisms. Emerging multidrug-resistant (MDR) strains possessing altered alleles (encoding PBP2) pose a global health emergency as they threaten the utility of ceftriaxone, the last remaining outpatient antibiotic.
View Article and Find Full Text PDFPotent EGFR/PARP-1 inhibition by spirooxindole-triazole hybrids for targeted liver cancer therapy.
RSC Adv
January 2025
Department of Chemistry, College of Science, King Saud University P. O. Box 2455 Riyadh 11451 Saudi Arabia
The search for effective anti-cancer therapies has led to the exploration of dual inhibition strategies targeting multiple key molecular pathways. In this study, we aimed to design a novel candidate capable of dual inhibition targeting both EGFR (Epidermal Growth Factor Receptor) and PARP-1 (poly(ADP-ribose)polymerase-1), two crucial proteins implicated in cancer progression and resistance mechanisms. Through molecular hybridization and structure-based drug design approaches, we synthesized a series of compounds based on spirooxindole with triazole scaffolds with the potential for dual EGFR and PARP-1 inhibition.
View Article and Find Full Text PDF1D CoMoC-Based Heterojunctional Nanowires from Pyrolytically "Squeezing" PMo/ZIF-67 Cubes for Efficient Overall Water Electrolysis.
Small
January 2025
Key Laboratory of Functional Inorganic Material Chemistry, Ministry of Education of the People's Republic of China, Heilongjiang University, Xuefu Road, Harbin, 150080, P. R. China.
The bi-transition-metal interstitial compounds (BTMICs) are promising for water electrolysis. The previous BTMICs are usually composed of irregular particles. Here, this work shows the synthesis of novel 1D CoMoC-based heterojunction nanowires (1D Co/CoMoC) with diameters about 50 nm and a length-to-diameter ratio about 20 for efficient water electrolysis.
View Article and Find Full Text PDFMolecular basis of human angiotensin-1 converting enzyme inhibition by a series of diprolyl-derived compounds.
FEBS J
January 2025
Department of Life Sciences, University of Bath, UK.
Angiotensin-1-converting enzyme (ACE) is a zinc-dependent carboxypeptidase of therapeutic interest for the treatment of hypertension, inflammation and fibrosis. It consists of two homologous N and C catalytic domains, nACE and cACE, respectively. Unfortunately, the current clinically available ACE inhibitors produce undesirable side effects due to the nonselective inhibition of these domains.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!